What Is Progesterone?

Progesterone is a naturally occurring steroid hormone classified as a progestin. It is used to prevent endometrial hyperplasia in postmenopausal women taking estrogen, treat secondary amenorrhea (absent periods), and support embryo implantation and early pregnancy in assisted reproductive technology (ART) procedures such as IVF.

Progesterone is available in several forms including oral capsules (brand name Prometrium), vaginal gels (Crinone), vaginal inserts (Endometrin), and intramuscular injections. It is also used off-label for luteal phase support in IVF cycles, prevention of preterm birth in women with a short cervix, irregular uterine bleeding, and premenstrual syndrome (PMS).

How does Progesterone work?

Progesterone binds to progesterone receptors in the uterus, transforming the proliferative endometrium into a secretory endometrium. This prepares the uterine lining for potential embryo implantation and supports the maintenance of early pregnancy. In menopausal hormone therapy, Progesterone counteracts the proliferative effects of estrogen on the uterine lining, reducing the risk of endometrial hyperplasia and cancer.

Oral capsules should be taken at bedtime on an empty stomach to minimize dizziness and drowsiness. Vaginal formulations deliver Progesterone directly to the uterus with fewer systemic side effects.

What doses are available for Progesterone?

• Oral capsule: 100 mg, 200 mg (Prometrium and generics)
• Vaginal gel: 4% (45 mg) and 8% (90 mg) — Crinone
• Vaginal insert: 100 mg — Endometrin
• Intramuscular injection: 50 mg/mL (Progesterone in oil)
• Compounded formulations: Vaginal suppositories and creams (various doses)

How hard is it to find Progesterone in stock?

Progesterone has a findability score of 55 out of 100, meaning it can be moderately difficult to locate in stock. ASHP has listed Progesterone capsules, injectable Progesterone, and vaginal inserts on active shortage lists. Capsule shortages involve select manufacturers, though Amneal and Virtus still have supply available. Injectable shortages stem from increased demand and manufacturing delays. Availability varies by formulation and region, so checking multiple pharmacies or using Medfinder is recommended.

Who Can Prescribe Progesterone?

Progesterone is commonly prescribed by several types of healthcare providers:

• Obstetricians and Gynecologists (OB/GYN): Most frequently prescribe Progesterone for menstrual irregularities, menopausal hormone therapy, and pregnancy support.
• Reproductive Endocrinologists: Prescribe Progesterone for IVF and fertility treatments, including luteal phase support.
• Primary Care and Family Medicine: May prescribe for hormone therapy or amenorrhea.
• Endocrinologists: Prescribe for hormonal conditions and imbalances.
• Internal Medicine: May manage menopausal hormone therapy including Progesterone.

Telehealth providers can also prescribe Progesterone for appropriate indications.

Is Progesterone a controlled substance?

No, Progesterone is not a controlled substance. It is not classified under any DEA schedule. However, it does require a prescription from a licensed healthcare provider. You cannot purchase Progesterone over the counter in prescription-strength formulations (though some low-dose OTC creams exist, they are different from prescription Progesterone).

Common Side Effects of Progesterone

Most side effects of Progesterone are mild and may include:

• Dizziness and drowsiness (especially with oral capsules)
• Headache
• Breast tenderness or pain
• Nausea and vomiting
• Bloating
• Mood swings and irritability
• Fatigue
• Joint or muscle pain
• Vaginal discharge (with vaginal formulations)
• Constipation or diarrhea

Serious side effects are rare but can include blood clots (DVT, pulmonary embolism), stroke, heart attack, severe allergic reactions, seizures, and severe depression. Contact your doctor immediately if you experience sudden chest pain, shortness of breath, severe headache, vision changes, or leg swelling.

Boxed Warning: Progestins used with estrogens in menopausal hormone therapy may increase the risk of cardiovascular disorders and breast cancer. Use the lowest effective dose for the shortest duration needed.

Alternative Medications to Progesterone

If you cannot find Progesterone in stock or need a different option, consider these alternatives (with your doctor's guidance):

• Medroxyprogesterone (Provera): A synthetic progestin used for amenorrhea, abnormal uterine bleeding, and menopausal hormone therapy. Available as oral tablets (2.5 mg, 5 mg, 10 mg). Generally lower cost but synthetic rather than bioidentical.
• Norethindrone (Aygestin): A synthetic progestin for amenorrhea, endometriosis, and abnormal uterine bleeding. Available as oral 5 mg tablets. Also available in low-dose form (0.35 mg) as a progestin-only contraceptive.
• Hydroxyprogesterone Caproate (Makena): An injectable progestin previously used for preterm birth prevention. FDA requested voluntary withdrawal in 2023 due to lack of confirmed efficacy; availability is very limited.
• Megestrol Acetate (Megace): A synthetic progestational agent primarily used for breast or endometrial cancer and appetite stimulation. Not a typical substitute for standard Progesterone therapy.

Drug Interactions with Progesterone

Progesterone can interact with several medications. Always tell your doctor about everything you take:

• Strong CYP3A4 inhibitors (Ketoconazole, Itraconazole, Clarithromycin): May increase Progesterone levels and side effects.
• Strong CYP3A4 inducers (Rifampin, Carbamazepine, Phenytoin, St. John's Wort): May decrease Progesterone levels, reducing effectiveness.
• Anticoagulants (Warfarin): Progesterone may alter blood clotting; monitoring may be needed.
• Moderate CYP3A4 inhibitors (Erythromycin, Fluconazole, Verapamil): May moderately increase Progesterone levels.
• Other hormonal medications (Estrogens, oral contraceptives): May have additive hormonal effects.
• Diabetes medications: Progesterone may affect glucose tolerance; blood sugar monitoring is advised.

Food interaction: Grapefruit juice may increase Progesterone levels. Oral capsules should be taken on an empty stomach at bedtime.

Final Thoughts on Progesterone

Progesterone is a widely used and essential hormone medication for women's health — from menopausal hormone therapy to fertility treatments and pregnancy support. While the current shortage can make it harder to find, generic Progesterone capsules remain affordable at $14–$30 with discount coupons, and multiple formulations give patients and providers options if one form is unavailable.

If you're struggling to find Progesterone in stock at your local pharmacy, use Medfinder to search real-time availability near you. Talk to your doctor about alternative formulations or medications if your usual form is out of stock.